Overdoses and smoking are taking the lives of people with HIV who have been cured of hepatitis C

• Researchers studied survival of Canadians co-infected with HIV and hepatitis C
• Cirrhosis-related deaths began to decline in 2013 with new hepatitis C treatments
• Overdose has now overtaken cirrhosis as the leading cause of death for this group

Hepatitis C virus (HCV) infects the liver and can cause chronic infection and inflammation in this vital organ. Over time, this inflammation causes the liver to replace healthy cells with useless scar tissue in a process called fibrosis. If chronic HCV infection is left untreated, scarring gradually spreads across the liver until most or all of this organ is scarred—a condition called cirrhosis. People with cirrhosis are at heightened risk for a range of complications, including severe fatigue, internal bleeding, recurring and serious abdominal infections and problems thinking clearly, as well as liver failure, liver cancer and death.

Over the past five years, highly potent and well-tolerated oral HCV treatments have become available in Canada and other high-income countries. In clinical trials, these drugs—called direct-acting antivirals (DAAs)—have resulted in cure rates of 95% and higher.

Researchers across Canada have been collaborating in a prospective observational study called the Canadian Co-Infection Cohort (code named CTN222). In this study, researchers have been monitoring the health of people co-infected with HIV and HCV.

In the latest analysis from this study, researchers examined trends in health and survival between two periods: 2003 to 2012 and 2013 to 2017. The study reported results from 1,634 people.

The researchers found that in the earlier period of the study, death from cirrhosis-related complications was common. However, in the latter part of the study, when DAAs became available, death from cirrhosis-related complications had declined. From 2013 to 2017, drug overdose was the leading cause of death in people aged 20 to 49. Among people aged 50 to 80, death from complications due to smoking was predominant.

The researchers outlined ways to improve the survival of people who have HCV or who have been cured of HCV.

Study details

Researchers analysed data from 1,634 co-infected people. As people who entered the study in the second period (2013 to 2017) are more reflective of co-infected people today, the average profile of these people upon entering the study was as follows:

• 72% men, 28% women
• Indigenous people – 24% (details on the ethno-racial composition of the rest of participants was not released in this report, but it is likely that a majority would be white)
• 80% had a history of injecting street drugs and about one-third currently injected street drugs
• 90% of participants had a history of smoking and 72% were current smokers
• CD4+ count – 450 cells/mm³
• HIV viral load – 90% had a viral load less than 50 copies/mL
• length of time infected with HCV – 20 years

Results

Over both periods studied (2003 to 2017), 273 people died (17%). Prior to their deaths, about 20% of people who died had disengaged from medical care.

People who died generally had the following factors in common vs. people who survived:

• were between the ages of 43 to 53 years
• had HCV infection for longer
• had a significant degree of fibrosis and/or a history of symptoms of cirrhosis
• had lower CD4+ cell counts (around 330 cells/mm³)
• were not likely to have a suppressed HIV viral load
• were engaged in injecting street drugs
• were smokers

Causes of death

Common causes of death in decreasing order were as follows:

• drug overdose
• complications arising from cirrhosis (also called end-stage liver disease, ESLD)
• smoking-related complications such as heart attack/stroke, pneumonia, cancers of the lungs and throat
• serious infections
• suicide/trauma/accidents

Deaths from AIDS-related complications were rare; only about 2% of such deaths occurred.

Note that despite a thorough review of records, researchers were unable to determine the cause of death in 20% of participants.

Trends

Upon comparing the two study periods—2003 to 2012 and 2013 to 2017—researchers found the following trends:

• Death rates remained stable among people aged 20 to 49 but decreased among people aged 50 to 80.
• Overall, death due to complications of cirrhosis decreased, particularly in people aged 50 to 80 years, and was no longer the leading cause of death.
• Although death from smoking-related complications generally decreased, smoking-related causes accounted for the most deaths in people aged 50 to 80.
• Among people aged 20 to 49, death due to overdose decreased somewhat. However, it still remained the leading cause of death in this age group.

Focus on cirrhosis

The researchers stated that the decrease in deaths from complications arising from cirrhosis is probably due to the following factors:

• the expansion of HCV treatment after 2013 (when DAAs started to become available)
• the more recent availability of highly potent DAAs
• the prioritization by doctors and nurses of treatment for people with a significant degree of liver fibrosis

The researchers stated that people with cirrhosis who have been cured of HCV will need continued monitoring, as their risk for liver cancer remains elevated.

In the study, nearly all deaths related to complications of cirrhosis occurred in people who were unable to be cured by DAAs.

Reducing death from overdose

Although an epidemic of deaths from opioids has been underway in North America, death from drug overdose among people aged 20 to 49 in the study decreased. According to the researchers, this decrease suggests “that improved linkage and access to harm reduction services may be occurring concurrently with HIV and HCV treatment.”

In another study, the same researchers found that once people are cured of HCV, about 10% of them who were previously injecting street drugs seem to stop injecting. The researchers stated that this reduction implies that “there may be indirect benefits associated with treatment centred around accessing harm reduction programs. However, such programs must be sustained after treatment to reduce re-infection and the harms of injecting street drugs.”

Smoking

The proportion of people in the present study who smoked was extremely high. The researchers found an overall reduction in smoking-related deaths during the course of the study. They propose that a partial explanation for this is the “prolonged engagement in care, with associated health promotion and availability of smoking cessation services.”

Larger issues

The researchers stated that in addition to the need for “universal access to HCV treatment,” there are additional issues that funders need to address, including the following:

• access to harm reduction services
• regulated opioid distribution programs
• drug treatment centres
• easy access to naloxone
• supportive housing programs

The researchers also stated that “providing HCV treatment alone while neglecting to concurrently address the social determinants of health will do little to improve the health outcomes of the majority of individuals with chronic HCV as [a previous study by the same team] has shown.”

—Sean R. Hosein

REFERENCES:

1. Kronfli N, Bhatnagar SR, Hull MW, et al. Trends in cause-specific mortality in HIV-Hepatitis C co-infection following hepatitis C treatment scale-up. AIDS. 2019; in press.
2. Tyndall M. Misplaced advocacy: What does better hepatitis C treatment really mean? CMAJ. 2015 Oct 20;187(15):1111-2.